1. Field of the Invention
The present invention relates a reflectance-absorption spectroscopy method for the in vivo characterization and imaging of chemical composition and molecular features in abnormal tissues that are present in but are not limited to vascular diseases such as atherosclerosis. Through the use of a broad-band photon source that emits light in the mid-infrared (MIR) region, reflectance spectrographs and reflectance generated absorption spectrographs of segments of normal tissues and tissues with chronic inflammatory conditions were collected and compared. A number of MIR spectral bands were identified as diagnostic markers for chronic inflammatory vascular conditions such as vulnerable plaques seen with atherosclerotic disease. These markers were used to develop a catheter-based diagnostic method and apparatus which use the broad-band MIR light or marker bands of MIR laser light for detecting and imaging disease tissues, particularly vulnerable lesions and other vascular diseases.
2. Related Art
Atherosclerosis is a common form of cardiovascular disease that leads to insufficient blood supply to critical body organs, resulting in heart attack, stroke, and kidney failure (Libby, P. Scientific American 2002, 286, 47-55). Atherosclerosis can also cause major complications in those suffering from hypertension and diabetes, as well as tobacco smokers. It is known that this form of the cardiovascular disease is the leading cause of death and disability in the developed world. In the United States alone, atherosclerosis is responsible for almost one million fatalities each year, which is more than one half of all deaths. In addition, almost 5 million persons are afflicted with cardiovascular disease and require hospitalization for corrective surgery each year. Among those receiving corrective surgery, almost one half would suffer in less than six months the recurrence of stenosis (an accelerated form of atherosclerosis or artery stricture) and even sudden cardiac deaths (Ross, R. Nature 1993, 362, 801-809), particularly in young men (Naghavi, M.; Madjid, M.; Khan, M. R.; Mohammadi, R. M.; Willerson, J. T.; Casscells, S. W. 2002, 30).
Such failure of coronary angiography in determining the clinical severity and in predicting future recurrence of acute coronary syndromes in symptomatic patients has driven scientists to develop new diagnostic methods for identifying vulnerable atherosclerotic plaques. Among them are the following promising technologies: contrast enhanced and intravascular magnetic resonance imaging (MRI), optical coherence tomography (OCT), electron-beam computed tomography (EBCT), angioscopy, elastography, intravascular ultrasound (IVUS), and fluorescence spectroscopy. With the exception of fluorescence spectroscopy (to some extend), these new methods aim at plaque structure/morphology or plaque activity/physiology; although there is overwhelming evidence that atherosclerotic plaques are not merely an accumulation of fat in the arterial wall. Medical research conducted (Chan, A. W.; Ross, J. Clinical & Investigative Medicine—Medecine Clinique et Experimentale 1997, 20, 320-326; Kaneko, E. et al., Coronary Artery Disease 2000, 11, 599-606; Forte, A. et al., A. Journal of Cellular Physiology 2001, 186, 307-313) and clinical observations (Davies, M. J.; Thomas, T. Philos Trans R Soc Lond Biol Sci 1981, 294, 225-229; Walts, A. E.; Fishbein, M. C.; Sustaita, H.; Matgloff, J. M. Circulation 1982, 65, 197-201; Falk, E. Br Heart J 1983, 50, 127-134) acquired in the past decade have revealed that atherosclerosis is indeed not a simple fat buildup at the arterial wall. Instead, it is an ongoing active disease caused by progressing atherosclerotic/vulnerable plaques, which are an evolving active collection of different migrated, proliferated, infiltrated cells (mainly smooth muscle cells and immune cells especially inflammatory macrophages), apoptotic/narcotic cells, along with one or more immune-triggering agents such as oxidized LDL and even infectious agents.
The most critical information needed for the accurate determination the clinical severity and reliable prediction of future recurrence of acute coronary syndromes in symptomatic patients is the microanatomic characteristics of plaque composition. A more promising in vivo diagnostic tool for preventive cardiology should be a method that enable an accurate identification and characterization in coronary patients of the plaques that are vulnerable to rupture in the future, i.e. “vulnerable plaque.”
Others in the art have recently attempted to provide Raman-based devices and techniques for diagnoses of tissues. Raman-based devices and techniques involve irradiating the tissue with light in the visible or near-infrared (NIR) regions of the electromagnetic spectrum, detecting light re-emitted (only about one per 107 incoming photons) by the tissue at the same frequency, or within a range of frequencies on one or both sides of the irradiating light, and determine the Raman shifted frequencies in the MIR region to diagnose the tissue's chemical conditions. An apparatus for the spectroscopic diagnosis of tissue conditions is described in Rava et al., in U.S. Pat. No. 6,697,665, and is hereby incorporated by reference. Richards-Kortum et al., in U.S. Pat. No. 6,095,982, describe methods and apparatus for detecting tissue abnormality through fluorescence or Raman spectroscopy after excitation of tissues in NIR wavelengths, and is also hereby incorporated by reference. Gellermann et al., in U.S. Pat. No. 6,205,354, described method and apparatus for the determination of levels of carotenoids and similar chemical compounds in biological tissue such as living skin.
Unlike the present invention, these Raman spectroscopy methods and apparatus are less sensitive to biomolecules with polar bonds and functional groups, which can be important during inflammation or in disease tissues. They also rely on the low intensity of re-emitting light (about one per 107 incoming photons) by the tissues, and often suffer interferences from background autofluorescence signals from tissues.